Effect of Iso-Caloric Substitution of Animal Protein for Other Macro Nutrients on Risk of Overall, Cardiovascular and Cancer Mortality: Prospective Evaluation in EPIC-Heidelberg Cohort and Systematic Review
Round 1
Reviewer 1 Report
Specific animal proteins have inverse association on all-cause and CVD mortality when plant protein are compared with for red and/or processed meat protein,. Isocaloric substitution of plant-based protein for animal-based protein might prevent all-cause and CVD-specific mortality.
As an essential macronutrient for humans, dietary protein plays a key role in maintaining physiological functioning and optimizing health span and longevity, mainly because of its favorable effect on weight management, strength, and maintaining cardiometabolic profile. In regard to the health effect of protein intake, substantial evidence has suggested that the source of protein and not only the amount of protein is important. Many studies reported that animal-based and plant-based protein had differential health effects: higher consumption of animal-based protein and major contributing food sources such as red and/or processed meat were associated with increased risk of cardiometabolic markers, weight gain, CVD, kidney diseases, gastrointestinal cancers and all-cause mortality, while higher intake of plant protein was linked to decreased risk of several aging-related outcomes including metabolic syndrome and its risk factors, cancer, CVD mortality, and all-cause mortality.
In this study, the authors used EPIC-Heidelberg (European Prospective Investigation into Cancer and nu-13 trition) to create iso-caloric substitution models and determined relative all-cause, cardiovascular, and cancer mortality hazards associated with dietary intake of animal protein and other macronutrient through Cox proportional hazard models. In addition, they also analyzed from a systematic review relating animal protein intake to mortality risk from seven prospective cohort studies in the USA, Europe, and Japan. Substitution of 3% of total energy from animal protein for fat and carbohydrate sub-types was associated with all-cause mortality (Hazard Ratios [HR] from 1.05 to 1.11), mostly driven by cardiovascular mortality. Independently of animal protein, substituting poly-unsaturated fat for saturated fat increased cancer-related mortality risk . This studu shows that ncreased cardiovascular and overall mortality risks in association with higher dietary intakes of animal protein largely such as previous iso-caloric modeling studies. Although many findings on reduced risk of all-cause, CVD and cancer mortality in association with substitution of plant protein for animal protein was consistent across various food sources of animal proteins and across different diseases, it is necessary to consider independent effects of specific protein intake as shown in this study. Moreover, given that the ideal isocaloric substitution of protein from different sources in an individual’s daily life was hard to achieve, this paper indicate that higher proportion of dietary energy from animal protein, combined with low energy intake from either carbohydrates or dietary fats, increases mortality risk. Crucially, animal protein was not the only macronutrient associated with increased mortality risk. Therefore, fthis provides accurate scientific evidence in this aspect by deriving the isoenergetic substitutional effects of animal and plant protein based on statistical modeling.
Author Response
RESPONSE TO REVIEWER 1
We thank the reviewer for this nice summary and overall evaluation.
Reviewer 2 Report
The manuscript is superb, refereeing to writing, the topic is although not extremely novel, quite actual, and the review included presents added value.
specific requested alterations:
Abstract: specify fat: total, SFA, PUFA or else, also carbohydrate sub-types, please specify
L39 for sugar, add added
L62-3 for ‘’ sub-types of dietary 62 protein, fats and carbohydrates’’ provide explanation, what do you mean by sub type of each macronutrient
L78 provide info for years of actual data collection
L99 provide reference for food atlas used
Do you have data for TFA intake? If yes, please provide, if not, add among limitations
L122 ‘’ tri-saccharides, higher oligosaccharides’’ use only the term oligosaccharides
L124 provide details about dates (years) of data collection
L134 what is smoking intensity? Please define i.e. use other wording for describing smoking habits/status
Author Response
REVIEWER 2 COMMENTS
Specific requested alterations:
- Abstract: specify fat: total, SFA, PUFA or else, also carbohydrate sub-types, please specify
Response: We have now listed the specific sub-types of fat and carbohydrate analyzed in the abstract.
- L39 for sugar, add “added”
Response: we have now added this word in L39.
- L62-3 for ‘’ sub-types of dietary 62 protein, fats and carbohydrates’’ provide explanation, what do you mean by sub type of each macronutrient
Response: We have now added the macronutrient sub-types in L62-3.
- L78 provide info for years of actual data collection
Response: In L78 we clarified that the actual data was collected between 1994 and 1998.
- L99 provide reference for food atlas used
Response: The photographs of food portion of various sizes used to increase the accuracy of portion size estimation were included in the questionnaire but unfortunately a reference to the food atlas is not available.
- Do you have data for TFA intake? If yes, please provide, if not, add among limitations.
Response: The information about TFA intake is available in our data. We have added the mean (and standard deviation) for energy intake from TFA, overall and by mortality status, to Table 1.
- L122 ‘’ tri-saccharides, higher oligosaccharides’’ use only the term oligosaccharides
Response: We have revised the term as ‘oligosaccharides’.
- L124 provide details about dates (years) of data collection
Response: In L124, we added that the prospective ascertainment of mortality endpoints were based on the complete case ascertainments from June 1994 until May 2019.
- L134 what is smoking intensity? Please define i.e. use other wording for describing smoking habits/status
Response: In L134, we updated the term smoking intensity to smoking history.
Note:
We realized an error in reference 18 and revised to include the correct reference. We extend our sincere apologies.
